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Background: Opioids prescribed to treat postsurgical pain have contributed to the ongoing opioid epidemic. While opioid prescribing practices have improved, most patients do not use all their pills and do not safely dispose of leftovers, which creates a risk for unsafe use and diversion. We aimed to generate consensus on the content of a "safe opioid use agreement" for the perioperative settings to improve patients' safe use, storage, and disposal of opioids. Methods: We conducted a modified three-round Delphi study with clinicians across surgical specialties, quality improvement (QI) experts, and patients. In Round 1, participants completed a survey rating the importance and comprehensibility of 10 items on a 5-point Likert scale and provided comments. In Round 2, a sub-sample of participants attended a focus group to discuss items with the lowest agreement. In Round 3, the survey was repeated with the updated items. Quantitative values from the Likert scale and qualitative responses were summarized. Results: Thirty-six experts (26 clinicians, seven patients/patient advocates, and three QI experts) participated in the study. In Round 1, >75% of respondents rated at least four out of five on the importance of nine items and on the comprehensibility of six items. In Round 2, participants provided feedback on the comprehensibility, formatting, importance, and purpose of the agreement, including a desire for more specificity and patient education. In Round 3, >75% of respondents rated at least four out of five for comprehensibility and importance of all 10 updated item. The final agreement included seven items on safe use, two items on safe storage, and one item on safe disposal. Conclusion: The expert panel reached consensus on the importance and comprehensibility of the content for an opioid use agreement and identified additional patient education needs. The agreement should be used as a tool to supplement rather than replace existing, tailored education. [ABSTRACT FROM AUTHOR]